The objective of this proposal is to determine the biochemical events associated with lipoprotein metabolism in the microvasculature, with particular emphasis on lipid metabolism by the endothelial cell. Most of the proposed studies will utilize rabbit cerebral microvessels, consisting predominantly of intact capillaries, arterioles and venules as a model system. Initially, methodology for the fractionation of microvessels into a capillary-enriched fraction will be developed and lipoprotein lipase activity will be assessed in such fractions. Additional studies will examine the hydrolysis of lipoprotein-associated triglyceride and cholesteryl ester by intact microvessels or cell-free fractions using radioisotopic techniques. In vivo studies will be performed in which labeled lipoproteins will be administered by intracarotid injection to determine the comparative uptake of labeled lipids by cerebral microvessels and selected regions of the brain. In addition, cholesterol turnover studies will be performed to determine the rate of equilibration between lipid metabolism in the microvasculature and atherogenesis, comparative studies between intact microvessels and aortic tissue will be undertaken in control and cholesterol-fed animals.